Project Summary/Abstract: People living with HIV (PLHIV) experience a disproportionately high symptom burden (e.g., fatigue, insomnia, pain) with few treatment options. These symptoms are frequent, distressing, often co-occur, and have significant consequences on the health and well-being of PLHIV, yet we know almost nothing about how to effectively mitigate them. Non-pharmacological treatment options are highly desirable for symptom management among PLHIV who already experience a high pill burden from multiple comorbid diseases. Our team previously reported that physical activity and better nutrition were associated with lower symptom intensity in PLHIV; but a clearer understanding of the effects of physical activity and diet is required to determine how these approaches can reduce symptom distress in this population. Building on these data, this project proposes to examine the effect of two promising non-pharmacological strategies, Physical Activity Routines And Dietary Intake, on the longitudinal Symptom Experience of PLHIV (PARADISE-HIV). The PARADISE-HIV study is an observational, longitudinal study that will utilize the substantial infrastructure of the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) to examine physical activity and dietary patterns and symptom burden of 850 PLHIV over four years. This study will occur in four demographically diverse HIV clinics [Case Western Reserve University (Cleveland, Ohio), University of Alabama at Birmingham (Birmingham, Alabama), University of Washington (Seattle, Washington) and Fenway Health Institute (Boston, Massachusetts)]. PARADISE-HIV will overcome the limitations of previous studies by 1) enrolling a large, demographically and geographically diverse, clinic-based sample of PLHIV, 2) examining the relationship between physical activity, dietary intake and symptom burden over time, and 3) using prospective, gold-standard measures of physical activity (i.e., triaxial accelerometry) and dietary intake (i.e., 24-hour diet recalls). Anthropomorphic and physical fitness factors will be assessed as potential mediators of physical activity and dietary intake on symptom burden and intensity. When our aims are accomplished we will have precise, definitive, high-quality data describing the impact of physical activity and diet on symptoms in PLHIV. These data can be used clinically to provide feedback to HIV health care providers on the physical activity and dietary intake of their patients. The PARADISE-HIV study will also have a significant scientific impact and will inform the next phase of this program of research. These findings will be used to develop an individually-targeted, clinic-based intervention to improve physical activity and dietary intake that will eventually reduce symptoms among PLHIV. They will also be used to examine biological and clinical mechanisms that lead to the prevalent unremitting symptoms experienced by PLHIV. Thus, the proposed study is likely to stimulate novel research that will have a long-term impact on the health and quality of life of PLHIV.